E. coli normally replicates its DNA with a very high degree of fidelity. It is not known whether this is achieved by the replicative DNA polymerase (polymerase III) alone, by the polymerase acting in concert with other proteins, or by the polymerase together with post-replication repair systems. One approach to sorting out this problem is to take a strain with a mutationally altered polymerase III which has been rendered mutagenic and look for mutations in the strain which show mutational synergy, that is, mutations which are strongly mutagenic when in the same strain with a polymerase III mutation, but show relatively little mutagenicity by themselves. Such mutants must interact directly or indirectly with polymerase III. Using a novel papillation technique a number of mutations which show a high degree of synergy with polymerase III have been isolated. Biochemical and genetic techniques will be used to determine whether these mutations are alleles of mutations known to affect DNA metabolism, thus suggesting a role in maintaining replicative fidelity for the corresponding wild-type protein, or are novel mutants affecting post-replication DNA repair.